Project Summary In thirty percent of patients with severe, drug-refractory heart failure, regional timing of myocardial contraction and relaxation is dyssynchronous. This mechanical dyssynchrony leads to adverse ventricular remodelling, increased mitral regurgitation, and reduced ejection fraction. Cardiac resynchronization therapy (CRT) is a relatively new treatment for heart failure patients with dyssynchrony that results in both acute hemodynamic benefit as well as improved long-term outcome. Despite CRT showing benefits in many multi- center clinical trials, 30% of patients selected for CRT show no improvement by clinical or echocardiographic endpoints. This poor response rate may in part be explained by limitations of current methods to determine the presence and severity of dyssynchrony. To overcome the limitations of existing dyssynchrony parameters, we have developed a new mathematical method to calculate a temporal delay between two myocardial tissue velocity profiles acquired with tissue Doppler imaging (TDI). Our method utilizes a function to quantify either systolic, diastolic, or whole- cycle delays using TDI data collected throughout the cardiac cycle. The objectives of this study are to evaluate the ability of our method to: 1) quantify mechanical dyssynchrony in the heart, and 2) predict response to CRT. Preliminary data in a group of young, healthy, normal subjects (negative controls) and known responders to CRT (positive controls) indicate excellent sensitivity and specificity of the methodology. The central hypothesis of this study is that our method of determining dyssynchrony delays is more sensitive and specific in selecting patients who respond to CRT compared to currently utilized methods. To test the hypothesis, we will utilize an existing data set of from a large, multi-center CRT trial (PROSPECT trial). The specific aims of this project are: 1) Quantify systolic, diastolic and whole-cycle delays in a group on normal, aged-matched subjects (negative controls) and compare delay values in these subjects to delay values in a group known responders to CRT (positive controls). 2) Evaluate the ability of systolic, diastolic, and whole-cycle delays to predict response to CRT using an existing large, multi-center database of 260 patients. Project Narrative We propose to develop and test a new method to improve selection of patients who will benefit from cardiac pacemaker implantation. The methodology uses signal processing methods based on echocardiographic image data. We will use images from an existing database of 260 subjects. The method would improve patient selection so only subjects who would benefit from pacemaker implantation would be identified, and all subjects who would benefit from a pacemaker would be identified.